Human cathelicidin LL-37 inhibits platelet aggregation and thrombosis via Src/PI3K/Akt signaling

• LL-37 inhibits platelet aggregation and thrombus formation.
• LL-37 attenuates the phosphorylation of Src/PI3K/Akt signaling.
• LL-37 decreases platelet spreading and inhibits P-selectin expression.

Biological functions of human cathelicidin LL-37 have been widely reported, including antibacterial, immune and anti-tumor effects. However, the antiplatelet activity of LL-37 has not been addressed. The purpose of our study was to investigate the antiplatelet and antithrombotic actions of LL-37. We found that this peptide inhibited human platelet aggregation in vitro and attenuated thrombus formation in vivo. Furthermore, LL-37 reduced phosphorylation of Src kinase and AktSer473, decreased platelet spreading on immobilized fibrinogen and inhibited P-selectin expression on platelets. These results demonstrate that LL-37 has antiplatelet and antithrombotic actions.